Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that is incurable and typically progressive. Chronic bronchitis and emphysema are the predominant examples of COPD. Most people diagnosed with COPD have both chronic bronchitis and emphysema. COPD is a leading cause of death worldwide, and its prevalence is increasing in the industrial countries (see, e.g., Lau et al., 2009, J Cell Physiol. 221:535-543; Devanarayan et al., 2010, COPD 7(1):51-58).
Symptoms of COPD include shortness of breath, chronic persistent coughing, chronic coughing that produces excessive amounts of mucus, chest tightness, and wheezing, among other symptoms. On a tissue level, COPD is characterized by inflammation, cell death and extensive lung tissue remodeling. Genetic markers have been studied as potential markers of early disease and prognosis in COPD. See, e.g., Dahl et al., 2009, Internatl J Chron Obstruct Pulmon Dis. 4:157-167. Changes in serum proteins, such as C-reactive protein (CRP) and surfactant proteins A and D, have been identified in COPD patients. See, for instance, Pinto-Plata et al., 2006, Thorax 61(1):23-28; Epub 2005 Sep. 2 and Lau et al., 2009, supra. To date, these changes in serum proteins have not been useful for predicting COPD susceptibility or severity.
Cigarette smoking is the leading risk factor for developing COPD. Other risk factors include cigar smoke, secondhand smoke and air pollution, as well as long term exposure to an excessive amount of dust, chemical fumes, smoke, gases, vapors or mists. Cigarette smoking has been shown to cause up-regulation in the lungs of proteins associated with the unfolded protein response, including GRP78, catreticulin, PDI and CHOP (Kelsen et al., 2008, Am J Respir Cell Mol Biol. 38:541-550; Tagawa et al., 2008 Free Rad Biol Med. 45:50-59). Other biomarkers have been indicated for COPD. See, e.g., U.S. Publication No. 2008/0044843 and WO 2009/114292. While risk factors are known, there is an on-going need to predict reliably which at-risk individuals will develop COPD. In addition, there is a need to predict reliably which COPD patients will experience rapid loss of lung function.
There is an unmet need for methods for assessing susceptibility to COPD development and to assess severity of disease in a COPD patient. The present disclosure addresses this need.